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The first studies of monoclonal B-cell lymphocytosis (MBL) in the general population were conducted as part of environmental health investigations that began in 1991. MBL was observed as an unexpected finding when blood samples were immunophenotyped by two-colour flow cytometric methods in common use at that time. The initial observations led to a workshop in 1995, at which case definitions were considered and medical follow-up investigations were recommended. Medical follow-ups were conducted in 1997 and 2003. A total of eight cases of confirmed MBL and three cases of presumptive MBL were identified. This review summarizes the findings from those investigations and discusses the issues related to using MBL as a biomarker in environmental health research and population-based studies.

This epidemiological study was conducted to determine whether high-resolution computed tomography (HRCT) is useful to screen for pulmonary abnormalities in people exposed to vermiculite containing asbestos. During June-September 2001, we evaluated HRCT of 353 people in Libby, MT, who had been exposed to asbestiform minerals associated with vermiculite. Of these, 334 participants of the summer 2000 medical testing program underwent HRCT of the chest at St. John's Lutheran Hospital and 19 eligible people who recently had undergone an HRCT scan at the same facility and under the same testing protocol allowed the study reviewers to use that scan. All 353 study participants were former vermiculite mine/mill workers (n = 55), their household contacts (n = 99), and people exposed to vermiculite through recreational or other activities (n = 199). Participants' 2000 medical testing results indicated only one of the three B-reader chest radiograph reviewers had reported a pleural abnormality (indeterminate chest radiograph). Three expert computer tomography (CT) scan evaluators reviewed the HRCT scans and identified pleural abnormalities in 98 (27.8%) of the 353 participants whose previous chest radiographs were classified indeterminate. Of these 98 people, 69 (70.4%) were either former vermiculite mine/mill workers or household contacts, and 40 (40.8%) showed pleural calcification on HRCT. Thirty out of the 40 people with pleural calcification reported having no occupational exposure to either Libby vermiculite or asbestos. Our findings indicate that low-dose HRCT can be considered for screening certain former vermiculite mine/mill workers and their household contacts who have indeterminate chest radiographs and may be useful for diagnosing a suspicious finding on a chest radiograph, particularly in a high-risk person.

Achieving the goal of increasing quality and years of healthy life is fundamentally based on success in the practice of public health. As our life style changes with time and as public health issues become more global, the practice of public health is enhanced to meet new challenges. In addition to addressing infectious diseases, environmental concerns are gaining attention. New challenges require the modification of the methods of investigations, use of new technologies and application of real-time management of public health emergencies. In many situations, collaborations at the local, regional, national and global levels are needed. This manuscript provides a summary of the approaches to address certain crucial environmental health concerns towards the goal of increasing quality and years of healthy life.

Mining, handling, processing, and personal or commercial use of asbestos-contaminated vermiculite have led to widespread contamination of the Libby, Montana, area. We initiated a medical testing program in response to reports of respiratory illness in the community. The purpose of this analysis was to identify and quantify asbestos-related radiographic abnormalities among persons exposed to vermiculite in Libby and to examine associations between these outcomes and participants' self-reported exposures. A cross-sectional interview and medical testing were conducted in Libby from July through November 2000 and from July through September 2001. A total of 7,307 persons who had lived, worked, or played in Libby for at least 6 months before 31 December 1990 completed the interview. Of those, 6,668 participants > or = 18 years of age received chest radiographs to assess the prevalence of pleural and interstitial abnormalities. We observed pleural abnormalities in 17.8% of participants and interstitial abnormalities in < 1% of participants undergoing chest radiography. We examined 29 occupational, recreational, household, and other exposure pathways in the analysis. The prevalence of pleural abnormalities increased with increasing number of exposure pathways, ranging from 6.7% for those who reported no apparent exposures to 34.6% for those who reported > or = 12 pathways. The factors most strongly associated with pleural abnormalities were being a former W.R. Grace worker, being older, having been a household contact of a W.R. Grace worker, and being a male. In addition to being a former W.R. Grace worker, environmental exposures and other nonoccupational risk factors were also important predictors of asbestos-related radiographic abnormalities.

We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers.

This study assessed the impact of environmental cadmium and lead exposure on the immune system of more than 2000 children and adults. Serum immunoglobulins [immunoglobulins (Ig) A, G, and M] and peripheral blood lymphocyte phenotypes (T cells, B cells, NK cells, and CD4/CD8 subsets) were measured in a total of 2041 children and adults who lived either in sites with elevated soil levels of cadmium and lead (n = 1561) or in comparison communities (n = 480). The blood lead and urine cadmium levels of participants were somewhat higher than national averages. Mean blood lead levels were 7 microg/dl for participants aged 6-35 mo; 6 microg/dl for participants aged 36-71 mo, 4 microg/dl for participants aged 6-15 yr; and 4.3 microg/dl for participants aged 16-75 yr. Multivariate analysis indicated no marked differences in any of the immune marker distributions attributed to lead for adults or children over 3 yr of age. However, in children under age 3, increased blood lead levels, principally those over 15 microg/dl, were associated with increases in IgA, IgG, IgM, and circulating B lymphocytes. Among adults, urine cadmium levels over 1.5 microg/g were associated with higher levels of IgA and circulating B lymphocytes. No evidence of immunosuppression was noted. The findings of potential immunologic effects at lead levels > 15 microg/dl in young children and at urine cadmium levels > 1.5 microg/g in adults are interesting, but too few participants had these high levels to delineate a threshold. Therefore, we find these results intriguing, but requiring confirmation in populations with higher exposure levels.

To identify kidney injury and dysfunction among persons exposed to hazardous substances in the environment, a battery of biomarker tests has been identified for systematic public health use. The standardized use of tests for conducting field epidemiology studies was reviewed in a 1995 joint American-European workshop, and recommended tests were selected by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC). These tests would be useful in conducting public health activities but are not recommended in a manner that would suggest changes in routine clinical practice. The tests selected include serum creatinine, urine analysis, urinary albumin, retinol-binding protein, N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and osmolality. Urinary creatinine was also included to adjust for urine concentration. The tests were chosen for use not only in epidemiologic field studies but also clinically oriented population screening and case studies of persons exposed to hazardous substances at waste sites. Studies using the battery may address the relationship between kidney damage and dysfunction and exposures to hazardous substances, especially in susceptible populations including children. Also, longitudinal studies should be conducted to evaluate the long-term health implications of abnormal tests and to measure the tests' predictive value for renal injury. These studies could evaluate the continuum of renal dysfunction as expressed by persistent decrements in glomerular filtration to the development of end-stage renal disease.

This paper estimates the health costs at Superfund sites for conditions associated with volatile organic compounds (VOCs) in drinking water. Health conditions were identified from published literature and registry information as occurring at excess rates in VOC-exposed populations. These health conditions were: (1) some categories of birth defects, (2) urinary tract disorders, (3) diabetes, (4) eczema and skin conditions, (5) anemia, (6) speech and hearing impairments in children under 10 years of age, and (7) stroke. Excess rates were used to estimate the excess number of cases occurring among the total population living within one-half mile of 258 Superfund sites. These sites had evidence of completed human exposure pathways for VOCs in drinking water. For each type of medical condition, an individual's expected medical costs, long-term care costs, and lost work time due to illness or premature mortality were estimated. Costs were calculated to be approximately $330 million per year, in the absence of any remediation or public health intervention programs. The results indicate the general magnitude of the economic burden associated with a limited number of contaminants at a portion of all Superfund sites, thus suggesting that the burden would be greater than that estimated in this study if all contaminants at all Superfund sites could be taken into account.

To identify neurotoxic effects in children living near hazardous waste sites, the Agency for Toxic Substances and Disease Registry (ATSDR) has designed a basic Pediatric Environmental Neurobehavioral Test Battery (PENTB) for children 1 through 16 years of age. It emphasizes tests appropriate to the stages of a child's development. These stages were fundamental factors in selecting tests for the PENTB, which includes both informant- and performance-based assessment procedures. Assessment of children under 4 years of age is restricted to four informant-based instruments, to evaluate as many functions as possible while minimizing testing time and the professional expertise needed in the test setting. The assessment of children 4 through 16 years of age includes 10 performance-based tests to evaluate key functions within the cognitive, motor, and sensory domains analogous to functions affected by neurotoxic chemicals in adults. In all age groups, it is crucial to also assess family, cultural, economic, and other potentially confounding variables.

Nationally recognized experts participated in a 3-day workshop to discuss the complex issues associated with neurobehavioral testing in environmental health settings, and to propose basic and focused test batteries for use in evaluating populations living near hazardous chemical sites. The Adult Environmental Neurobehavioral Test Battery (AENTB), which evaluates major neurobehavioral domains and functions, was adopted by the Agency for Toxic Substances and Disease Registry (ATSDR) for use as a basic screening panel in field studies. Pilot testing of the AENTB demonstrated an examiner training requirement of 3-6 practice sessions, a mean total testing time of 58.0 min (SD = 9.6), and, for 9 of the component tests, a sample size requirement of fewer than 140 (alpha = 0.05, 95% power) to detect a 20% difference between study groups. ATSDR administered the AENTB to 467 persons, selected randomly from 1,382 participants in field study sites in three states. Total testing time varied noticeably by participant age and study site, suggesting an ongoing need for site-specific controls in each field study using the AENTB. Also planned is adoption of a pediatric test battery to evaluate the domains and functions most relevant at major stages of child development.

Recall bias was assessed in a study of cancers reported by persons living in a community with a hazardous waste treatment facility (A) and a control community (B). The self-reported cancers were verified against medical records and pathology reports. Of the 56 cancer cases reported, 43 were in community A and 13 were in community B. The difference in incorrect reporting of neoplasms between community A and community B was 12% for neoplasms and 23% for malignancies. Before verification, there was a borderline significant association (P = 0.049) between living in community A and all self-reported cancers [odds ratio (OR) 1.88, 95% confidence interval 0.99-3.57]. The verified data showed that ORs decreased with the increasing precision of diagnosis. The effect of misclassification on the OR was an inflation by 15% for neoplasms and by 31% for malignancies. The results demonstrate the importance of verifying reported cases of disease, even a disease as well defined as cancer.

The Agency for Toxic Substances and Disease Registry (ATSDR) report "The Public Health Implications of Medical Waste: A Report to Congress" has been finalized and submitted to Congress. The report is a comprehensive review of all available data and information on the subject. Based on the data developed in the report, ATSDR concludes that the general public is not likely to be adversely affected by medical waste generated in the traditional health setting. However, the increase of in-home health care and other sources of nonregulated medical waste (e.g., intravenous drug users) provides opportunities for the general public to contact medical waste. In addition, ATSDR concludes that public health concerns exist for selected occupations involved with medical waste. These populations include janitorial and laundry workers, nurses, emergency medical personnel, and refuse workers. The ATSDR report also defines what material should be managed as medical waste and identifies research needs related to medical waste.

Information about human exposures to environmental agents is a crucial component of informed decisions about protection of public health. Results from an inventory of exposure-related databases are used to examine the value of exposure information for risk assessment, risk management, surveillance of status and trends, and epidemiologic studies. Findings indicate that current and future exposure-related databases should include (1) standardized procedures for the collection, storage, analysis, and reporting of data; (2) an enhanced ability to compare data over time, i.e., conduct comparison studies of "old" and "new" methods; (3) mechanisms for coordination and cooperation among public and private-sector organizations with respect to the design, maintenance, exchange, and review of information systems; (4) measurements of actual exposures and dose for relevant human populations; and (5) data collection, storage, and retrieval methods that permit easy manipulation of information for both model building and testing.

Exposure databases are useful for monitoring status and trends in environmental health. However, other supporting data are usually needed to infer human exposure or internal dose. Program planning and evaluation, environmental health surveillance, epidemiologic research, and contributions to international efforts are four major purposes for monitoring environmental exposure status and trends. Although databases play an important role in monitoring human exposure, certain methodological problems need to be overcome. The work group developed six criteria for meeting information needs for human exposure assessment. Areas that need attention are (1) specification of location, (2) specification of facility and chemical identifiers, (3) documentation of special populations at risk, (4) provision of early warning of new problems, (5) monitoring changes over time, and (6) enhancement of documentation. We tested these criteria by examining six available databases that might be used for monitoring exposure to contaminants in drinking water. Available data fell short of information needs. We drew four conclusions and offered several recommendations for each. First, available data systems lack adequate measures of human exposure. Second, data for monitoring exposures for many important population subgroups and environmental settings are inadequate. Third, an "early warning" system that monitors human exposures is needed. Fourth, designers of data-collection systems should consider the needs of users who monitor status and trends of human exposure.

Tornadoes in North and South Carolina on 28 March 1984 caused 252 people to be injured seriously enough to require hospitalization and 59 to be killed. To evaluate risk factors, we gathered information on 238 (94%) of those hospitalized and 46 (78%) of those killed. Those hospitalized or deceased had statistically significantly more deep cuts, concussions, unconsciousness and broken bones than those with them at the time of the tornado who were not hospitalized or killed. People living in mobile homes were more likely to be hospitalized or die than people occupying conventional houses. Other risk factors for hospitalization or death included advanced age (60+ years), no physical protection (not having been covered with a blanket or other object), having been struck by broken window glass or other falling objects, home lifted off its foundation, collapsed ceiling or floor, or walls blown away. More awareness of the tornado risk before it strikes and better adherence to tornado protection guidelines could reduce injuries and deaths in the future.

Improper dumping and storage of hazardous substances and whether these practices produce significant human exposure and health effects are growing concerns. A sequential approach has been used by the Centers for Disease Control and the Agency for Toxic Substances and Disease Registry in investigating potential exposure to and health effects resulting from environmental contamination with materials such as heavy metals, volatile organic compounds, and pesticide residues at sites throughout the United States. The strategy consists of four phases: site evaluation, pilot studies of exposure or health effects, analytic epidemiology studies, and public health surveillance. This approach offers a logical, phased strategy to use limited personnel and financial resources of local, State, national, or global health agency jurisdictions optimally in evaluating populations potentially exposed to hazardous materials in waste sites. Primarily, this approach is most helpful in identifying sites for etiologic studies and providing investigative leads to direct and focus these studies. The results of such studies provide information needed for making risk-management decisions to mitigate or eliminate human exposures and for developing interventions to prevent or minimize health problems resulting from exposures that already have occurred.

Outbreaks of staphylococcal skin infections among healthy adults are most unusual. The authors report an epidemic of skin infections due to Staphylococcus aureus that involved river rafting guides in Tennessee, South Carolina, and North Carolina in summer 1982. Infections occurred only among employees of the rafting companies that provided communal, on-site housing; carriage rates of S. aureus were as high as 89% at those companies. A case-control study found that having had an infected roommate was significantly associated with infection, as was working at the livery with the most crowded housing. This outbreak appeared to be due to two factors: frequent minor skin wounds acquired while rafting, and prolonged close contact among the persons with wounds. It is likely that crowding and exposure to infected wounds led to elevated S. aureus carriage rates, which in turn increased the probability that wounds would become infected. Repeated immersion in water likely enhanced the development of infections.